There is a trend in the chemical and biochemical sciences towards miniaturization of systems for performing analytical tests and for carrying out synthetic reactions, where large numbers of reactions must be performed. For example in screening for new drugs as many as 100000 different compounds need to be tested for specificity by reacting with suitable reagents.
Another field is polynucleotide amplification, which has become a powerful tool in biochemical research and analysis, and the techniques therefor have been developed for numerous applications. One important development is the miniaturization of devices for this purpose, in order to be able to handle extremely small quantities of samples, and also in order to be able to carry out a large number of reactions simultaneously in a compact apparatus.
In most systems for the purposes indicated above (and others not mentioned) there would commonly be a need for heating the reagents in some stage of the procedure for carrying out the necessary reactions. Even more importantly there is also a need for maintaining the reaction temperature at a constant level during a desired period of time, i.e. to avoid variations in temperature across the channel part containing the reagents that have been heated (reactor volume).
Furthermore, in these miniaturized systems the temperature of the sample will essentially be determined by the temperature of the wall confining the sample. Thus, if the material constituting the wall leads away heat, there will be a temperature drop close to the wall, and a variation throughout the sample occurs.
There is also a problem with evaporation when heating small aliquots of liquids within micro channel structures. This problem can be solved by providing heating means in the form of a surface layer that is capable of absorbing light energy for transport into a selected area. See WO 0146465 (FIG. 7 and related disclosure). Conveniently white light is used, but for special purposes, monochromatic light (e.g. laser) can also be used. The layer can be a coating of a light-absorbing layer, e.g a. black paint, which converts the influx of light to heat.
An alternative solution to the evaporation problem has been to carry out the steps involving elevated temperature (heating steps) within closed reaction volumes. This has required solving problems related the large pressure increase that typically is at hand when heating liquid aliquots without venting. If the process concerned is integrated into a sequence of reactions there is a demand for smart valving solutions.
In many of the prior art devices the substrate material has had a fairly high thermal conductivity which has permitted heating by ambient air or by separate heating elements in close association with the inner wall of the channel containing a liquid to be heated. Cooling has typically utilized ambient air. Recently it has become popular to manufacture micro channel structures in plastic material that typically has a low thermal conductivity. Due to the poor thermal conductivity, unfavorable temperature gradients may easily be formed within the selected area when this latter type of materials is used. These gradients may occur across the surface and downwards into the substrate material. The variation in temperature may be as high as 10° C. or more between the center of the area or region and its peripheral portions. If the light absorbing area is too small this variation will be reflected in the temperature profile within a selected area and also within the heated liquid aliquot. For many chemical and biochemical reactions such lack of uniformity can be detrimental to the result, and indeed render the reaction difficult to carry out with an accurate result.
Although the heating means according to WO 0146465 eliminates the evaporation and the pressure problem, it still suffers from the above-mentioned temperature variation across the sample. Such temperature variations are often detrimental to the outcome of a reaction and must be avoided.
Microfluidic platforms that can be rotated comprising heating elements have been described in WO 0078455 and WO 9853311. These platforms are intended for carrying out reactions at elevated temperature, for instance thermal cycling.